Functional nucleic acids, such as siRNAs, nucleic acid aptamers, and decoy nucleic acids, have drawn attention as pharmaceuticals or diagnostic agents in recent years, and research on and development of various nucleic acid drugs and the like are ongoing with the goal of establishing medical applications thereof all over the world.
The general problem of nucleic acids, however, is that these nucleic acids are likely to be degraded by nucleolytic enzymes, such as nucleases, in vivo. In vivo stabilization of the nucleic acids is essential problem for nucleic acid drugs to exert the pharmacological effects efficiently and continuously.
For improving the stability of nucleic acid aptamers against nucleolytic enzymes, a general approach involves chemically modifying sugar or phosphate portions, which are the backbones of nucleic acid, molecules (Non Patent Literatures 1 and 2 and Patent Literature 1). The problems of these modifications, however, are that the modifications might also influence the higher-order structure or physical properties of the nucleic acids; and the modifications might not only cause reduction in the capacity to bind to a target molecule or higher in vivo toxicity but increase production cost. Accordingly, under the present circumstances, it requires to modify modifiable sites, exhaustively screen them, and individually analyze them in order to practically use chemically modified nucleic acid aptamers as pharmaceuticals. Also, it is generally difficult to improve the capacity to bind to a target molecule by such chemical modifications, and there have been few reports thereon.
Thus, a convenient and low-cost method for enhancing the stability of a nucleic acid aptamer and further improving its capacity to bind to a target molecule has been demanded.